骨質疏松中衰老相關分泌表型調控機制的研究進展

楊超富 譚國慶 徐展望

基金項目：國家自然科學基金面上項目（82174410）；山東省自然科學基金資助項目（ZR2020KH011）；山東省自然科學基金面上項目（ZR2020MH362）；全國名老中醫專家傳承工作室建設項目（國中醫藥人教函［202275號］）

引用本文：楊超富，譚國慶，徐展望.骨質疏松中衰老相關分泌表型調控機制的研究進展［J］. 中國全科醫學，2024，27（29）：3685-3695. DOI：10.12114/j.issn.1007-9572.2023.0721. ［www.chinagp.net］

YANG C F，TAN G Q，XU Z W. Research progress on the regulation mechanism of aging-related secretory phenotype in osteoporosis［J］. Chinese General Practice，2024，27（29）：3685-3695.

? Editorial Office of Chinese General Practice. This is an open access article under the CC BY-NC-ND 4.0 license.

【摘要】 衰老相關分泌表型（SASP）是細胞衰老的重要特征，在調控疾病微環境中具有重要作用。目前，對于SASP干預骨代謝、誘導骨流失的作用機制了解有限，因此，本文探討了在骨質疏松模型中SASP的調控機制，并歸納總結了其調控特點：SASP在衰老骨細胞中充分表達，以自分泌/旁分泌的方式將衰老效應傳遞到間充質干細胞，從而干預其成骨分化；SASP激活免疫細胞，并促進其衰老，從而誘導炎性組織微環境的形成，加重骨流失；線粒體穩態失調、病理性血糖升高、肥胖誘導的脂肪蓄積均會促進SASP的表達，從而擾亂微環境穩態，將衰老效應傳遞到骨組織。所以，有必要深入了解SASP在骨質疏松中的作用，為后續開發抗SASP療法治療骨質疏松提供借鑒。

【關鍵詞】 骨質疏松；衰老相關分泌表型；細胞衰老；代謝紊亂；免疫調節

【中圖分類號】 R 681 【文獻標識碼】 A DOI：10.12114/j.issn.1007-9572.2023.0721

Research Progress on the Regulation Mechanism of Senescence-associated Secretory Phenotype in Osteoporosis

YANG Chaofu1，TAN Guoqing2*，XU Zhanwang2

1.Shandong University of Traditional Chinese Medicine，Jinan 250039，China

2.Spinal Department，Affiliated Hospital of Shandong University of Traditional Chinese Medicine，Jinan 250013，China

*Corresponding author：TAN Guoqing，Associate chief physician/Associate professor；E-mail：yxkmt@hotmail.com

【Abstract】 Senescence-associated secretory phenotype（SASP） is an important feature of cellular senescence and plays an important role in regulating the disease microenvironment. At present，the role of SASP in intervening bone metabolism and inducing bone loss is very limited. Therefore，this paper discusses the regulatory mechanism of SASP in osteoporosis models and summarizes its regulatory characteristics：SASP is fully expressed in senescent bone cells and transmits aging effects to mesenchymal stem cells in an autocrine/paracrine manner，thereby interfering with osteogenic differentiation. SASP activates immune cells and promotes their aging，thus inducing the formation of inflammatory tissue microenvironment and aggravating bone loss. Mitochondrial homeostasis，pathologic hyperglycemia，and obesity-induced fat accumulation all promote SASP expression，thus disrupting microenvironmental homeostasis and transmitting aging effects to bone tissue. To sum up，understanding the role of SASP in osteoporosis lays a solid foundation for us to develop anti-SASP therapy for osteoporosis in the future.

【Key words】 Osteoporosis；Senescence-associated secretory phenotype；Cell senescence；Metabolic disorders；Immunomodulation

骨質疏松癥是一種因骨密度下降導致骨折風險增高的全身性代謝骨病。2021年，一項全國性、多中心的雙能X線吸收測定法（DXA）研究調查了中國40歲以上人群骨質疏松癥的標準化患病率，該項研究顯示：40歲及以上女性骨質疏松癥的總體患病率為20.6%，男性為5.0%。……